Tumor Biology

, Volume 35, Issue 3, pp 2069–2074 | Cite as

RETRACTED ARTICLE: MicroRNA-128 promotes proliferation in osteosarcoma cells by downregulating PTEN

Research Article

Abstract

MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. Several studies have indicated that abnormal expression of miRNAs occurs frequently in human osteosarcoma. In the present study, we found that miR-128 expression was significantly increased in osteosarcoma tissues compared to adjacent normal tissues. Ectopic overexpression of miR-128 significantly promoted while suppression of miR-128 by its antisense inhibited the proliferation of MG63 and U2OS cells. At the molecular level, our results demonstrated that miR-128 overexpression could repress expression of PTEN by directly targeting PTEN 3'-untranslated region. Consistently, downstream AKT signaling was altered by miR-128 overexpression or knockdown. Therefore, our results suggest that miR-128 plays an important role in the proliferation of human osteosarcoma cells by directly regulation of PTEN/AKT signaling.

Keywords

Osteosarcoma MicroRNA Cell proliferation miR-128 PTEN 

Notes

Acknowledgments

This work was partially supported by National natural science foundation 81171705.

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. 1.
    Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;14(8):535–48.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol. 2013;14(8):475–88.CrossRefPubMedGoogle Scholar
  3. 3.
    van Kouwenhove M, Kedde M, Agami R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer. 2011;11(9):644–56.CrossRefPubMedGoogle Scholar
  4. 4.
    Kasinski AL, Slack FJ. Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy Nat Rev Cancer. 2011;11(12):849–64.PubMedGoogle Scholar
  5. 5.
    Liang W, Gao B, Fu P, Xu S, Qian Y, Fu Q. The miRNAs in the pathogenesis of osteosarcoma. Front Biosci. 2013;18:788–94.CrossRefGoogle Scholar
  6. 6.
    Cai CK, Zhao GY, Tian LY, Liu L, Yan K, Ma YL, et al. miR-15a and miR-16-1 downregulate CCND1 and induce apoptosis and cell cycle arrest in osteosarcoma. Oncol Rep. 2012;28(5):1764–70.PubMedGoogle Scholar
  7. 7.
    Huang G, Nishimoto K, Zhou Z, Hughes D, Kleinerman ES. miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression. Cancer Res. 2012;72(4):908–16.CrossRefPubMedGoogle Scholar
  8. 8.
    Peng DX, Luo M, Qiu LW, He YL, Wang XF. Prognostic implications of microRNA-128 and its functional roles in human epithelial ovarian cancer. Oncol Rep. 2012;27(4):1238–44.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, et al. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 2010;11(2):136–46.CrossRefPubMedGoogle Scholar
  10. 10.
    Liu J, Lu KH, Liu ZL, Sun M, De W, Wang ZX. MicroRNA-128 is a potential molecular marker of non-small cell lung cancer and functions as a tumor suppressor by targeting polo-like kinase 1. BMC Cancer. 2012;12:519.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Chen P, Zhao X, Ma L. Downregulation of microRNA-128 correlates with tumor progression and poor prognosis in hepatocellular carcinoma. Mol Cell Biochem. 2013 Jul 11, in pressGoogle Scholar
  12. 12.
    Petrelli A, Perra A, Schernhuber K, Cargnelutti M, Salvi A, Migliore C, et al. Sequential analysis of multistage hepatocarcinogenesis reveals that miR-128 and PLK1 dysregulation is an early event maintained along tumor progression. Oncogene. 2012;31(42):4517–26.CrossRefPubMedGoogle Scholar
  13. 13.
    Gebeshuber CA, Martinez J. miR-128 suppresses IGF2 and inhibits breast tumorigenesis by interfering with proliferation and survival signaling. Oncogene. 2013;32(27):3306–10.CrossRefPubMedGoogle Scholar
  14. 14.
    Bai J, Guo A, Hong Z, Kuai W. Upregulation of microRNA-128 predicts poor prognosis in patients with pediatric acute myeloid leukemia. Onco Targets Ther. 2012;5:213–9.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Zheng YS, Zhang H, Zhang XJ, Feng DD, Luo XQ, Zeng CW, et al. MiR-128 regulates cell differentiation and survival by targeting RBSP3, a phosphatase-like tumor suppressor in acute myeloid leukemia. Oncogene. 2012;31(1):80–92.CrossRefPubMedGoogle Scholar
  16. 16.
    Zheng YS, Zhang H, Zhang XJ, Feng DD, Luo XQ, Zeng CW, et al. MiR-128 regulates cell differentiation and survival by targeting RBSP3, a phosphatase-like tumor suppressor in acute myeloid leukemia. Oncogene. 2012;31(1):80–92.CrossRefPubMedGoogle Scholar
  17. 17.
    Lau LF. CCN1/PTEN: the very model of a modern matricellular protein. Cell Mol Life Sci. 2011;68(19):3149–63.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Lee KB, Byun HJ, Park SH, Park CY, Lee SH, Rho SB. PTEN controls p53 and NF-κB expression through PI3K/Akt/mTOR pathways in carboplatin-induced ovarian cancer cells. Cancer Lett. 2012;315(1):86–95.CrossRefPubMedGoogle Scholar
  19. 19.
    Goodwin CR, Lal B, Zhou X, Ho S, Xia S, Taeger A, et al. PTEN mediates hepatocyte growth factor-dependent tumor cell growth, migration, and Akt activation. Cancer Res. 2010;70(7):2932–41.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Lin J, Huo R, Wang L, Zhou Z, Sun Y, Shen B, et al. A novel anti-PTEN antibody inhibits breast cancer growth and metastasis in vivo. Cancer Immunol Immunother. 2012;61(5):677–87.CrossRefPubMedGoogle Scholar
  21. 21.
    Tsai MS, Bogart DF, Li P, Mehmi I, Lupu R. Expression and regulation of PTEN in human breast cancer cell lines. Oncogene. 2002;21(6):964–73.CrossRefPubMedGoogle Scholar
  22. 22.
    Leask A. CCN1: a novel target for pancreatic cancer. J Cell Commun Signal. 2011;5(2):123–4.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Haque I, Mehta S, Majumder M, Dhar K, De A, McGregor D, et al. PTEN/CCN1 signaling is critical for epithelial-mesenchymal transition and stemness and promotes pancreatic carcinogenesis. Mol Cancer. 2011;10:8.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Xie JJ, Xu LY, Xie YM, Du ZP, Feng CH, Dong H, et al. Involvement of PTEN in the growth, invasiveness and adhesion of esophageal squamous cell carcinoma cells. Int J Mol Med. 2011;27(3):429–34.PubMedGoogle Scholar
  25. 25.
    Sabile AA, Arlt MJ, Muff R, Bode B, Langsam B, Bertz J, et al. PTEN expression in osteosarcoma indicates poor prognosis and promotes intratibial growth and lung metastasis in mice. J Bone Miner Res. 2012;27(1):58–67.CrossRefPubMedGoogle Scholar
  26. 26.
    Fromigue O, Hamidouche Z, Vaudin P, Lecanda F, Patino A, Barbry P, et al. PTEN downregulation reduces osteosarcoma cell invasion, migration, and metastasis. J Bone Miner Res. 2011;26(7):1533–42.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.Department of Orthopaedic Surgery, Xinhua HospitalShanghai JiaoTong University School of MedicineShanghaiPeople’s Republic of China

Personalised recommendations